Causes of Prion Diseases

Causes of Prion Diseases Prion diseases or transmissible spongiform encephalopathys can be inheritable or transmissible, a common feature of the prion disease involves the change of the prion protein (PrPc) to the isoform PrPsc (Hu et al, 2007). Prion propagation involves a mechanism that changes PrPc to PrPsc in an autocatalytic way (Harris and True, 2006). PrPc is said to be the normal prion protein and PrPsc the scrapie isoform which is the mutagenic Prion protein said to be the un-normal form. Prion diseases can occur in both humans and animals, an though in humans they are particularly rare (Hur et al, 2002). They are known to be fatal neurodegenerative diseases (Hur et al, 2002). Hur et al (2002) said that the reason that there has become an increased interest in Prion diseases in science and health is because they are biologically different in their features compared with other known neurodegenerative diseases and that there are many gaps in the knowledge of prion diseases, for example the pathogenesi s, what causes the mutagenic prion protein and where prion diseases first arose from . The PrPsc isoform which is known to be the most common feature of the prion disease is dominated by a beta sheet containing strong hydrogen bonds and this structure is twisted, many researchers have found that the strong hydrogen bonds make this isoform resistant to digestion protein kinase k meaning that this protein can build up particularly in the brain tissue causing neuronal damage and therefore possibly leading to prion diseases. (Harris and true, 2006). Hu et al (2007) said that because the PrPsc isoform is protein kinase k resistant it isnt broken down and therefore increasingly accumulates in the brain tissue of patients with prion diseases and causes further neurodegeneration. Neurodegenerative diseases commence from the build up and the wrong conformational folding of a protein, the biological activity of a protein depends on its correct folding in the native conformation (Soto et al, 2002). Strong evidence has been shown that protein misfolding plays a major role in transmissible spongiform encephalopathy pathogenesis (Soto et al, 2002). There are many different types of prion diseases that have been found in both humans and animals one example includes Creutzfeldt-Jakob disease and another example is Kuru (Hu et al, 2007). Examples of prion diseases concerned with animals include scrapie. Bovine spongiform encephalopathy is also an animal prion disease which is also referred to as mad cow disease (Hu et al, 2002). Different forms of prion diseases both human and animal forms are associated with different forms of PrPsc (Soto et al, 2002). Many mutations in the PrPsc protein in prion disease have been found and linked to the different forms of Prion disease. The polymorphism at codon 129 has been found to play a major role in the phenotypic expression of Creutzfeldt-Jakob disease which is the most frequent type of Prion disease (Mikol, 1999). Mutations and insertions have been found to be involved in another from of human prion disease known as familial Creutzfeldt-Jakob Disease (Mikol 1999). A common mutation at cod on 178 had been found in the first case. Kuru is an acquired from of the prion disease, this can be characterised by kuru plaques which have been found in seventy percent of cases (Mikol, 1999). There has become recent interest in the kuru disease because of an increased resistance to this diseases. Kuru has the characteristic of quickly degenerating the central nervous system and it is fatal (Goldfarb, 2002). There was an outbreak of kuru which killed many people in new guinea most of these people were from a small area populated by a culture known as fore people (Goldfarb, 2002). It is not widely known how Prion diseases first developed in humans and animals but it is thought that kuru became transmitted to humans via cannibalism (Goldfarb, 2002). It was pursued in this culture to eat relatives who had died , therefore resulting in human to human transmission (Mead et al, 2009). By the late 1950s there was a stop to cannibalism and correlating with this the umber of people dying w ith kuru decreased also no person after the `1950,s had developed Kuru (Goldfarb, 2002). However how kuru first appeared in the fore people is still unclear, but a conclusion has been made that the kuru epidemic must have started with a single person who died from Creutzfeldt-Jakob disease and then was eaten by traditional cannibalism . Many studies have aimed to find the mutations involved in Kuru. The methionine/valine variation encoded by the 129 codon in the PRNP gene has been recorded in many Kuru patients, a recent study has shown that the 129 genotype is associated with an increased vunerability to Kuru (Goldfarb, 2002). Goldfarb 2002 found that in the fore culture the 129 genotype methionine/methionine was the most common in patients suffering from Kuru at an early age and that a change to methionine/valine showed that Kuru developed at a later age. Methionine/valine, valine/valine carriers survived the Kuru epidemic, codon 129 heterogeneity is thought to therefore be a resi stance factor for Kuru disease (Mead et al, 2009). Mead et al also studied another polymorphism which was thought to be linked to kuru, the G127V polymorphism. They concluded that this G127V gene is an agent gained that provides resistance to Kuru in a heterogeneous state and isnt a mutation which could have caused the Kuru epidemic (Mead et al, 2009). Many hypothesise have been developed in order to try and explain prion diseases, however none have been fully accepted. The most common hypothesis is the Prion hypothesis which suggests that the agent causing neurodegeneration is the prion protein but the mutagenic form which escapes protein kinas k digestion and remains in brain tissue causing neuronal damage (Yull et al, 2008).The Prion hypothesis states that the infectious agent of prion diseases is an abnormally folded isoform of the prion protein (PrPsc) that replicates its abnormal conformation (Baskakov and Breydo, 2006). Strong evidence has been shown that protein misfolding has a major role in transmissible spongiform encephalopathy pathogenesis (Soto et al, 2002). A number of hypotheses have been made in order to try and explain the pathogenesis of prion diseases, they all correlate to the prion protein hypothesis indicating that the mutated prion protein PrPsc is involved in the pathogenesis. One hypothesis links the pathogenesis to oxidative stress and suggests that PrPc is involved in making sure that cells dont become damaged by oxidative stress (Westergard, 2007). The change in the function of PrPc for example by a mutation/ misfolding may therefore be linked to the role in disease (Westergard, 2007). Oxidants are produced as the result of another action in respiration usually via abnormal anaerobic respiration in many people with neurodegenerative diseases (Hur et al, 2002). Levels of MDA can indicate oxidative stress, this is a reactive aldehyde which causes toxic stress in cells and as a result generates the production of free radicals, levels, levels of MDA have been found a higher levels in scrapie infected mice showing an involvement of oxidative stress (Hur et al, 2002).. It has therefore been suggested that the normal prion protein PrPc protects cells from oxidative stress and therefore an abnormal form of this protein will allow oxidative stress and therefore cause damage to neurones and therefore leading to prion diseases (Westergard, 2007). Evidence has also been found that the PrPc protein has SOD (Superoxide dimutase) activity and that the PrPc uses detoxification to remove any reactive oxygen species that could cause oxidative damage in cells, however other studies have found evidence against this therefore further work needs to be done to confirm this. One way that the PrPc protein has been found to stop oxidative damage is indirectly by increasing the cell components such as proteins, for example a combination of copper-zinc SOD that can remove and damage and circulating reactive oxidative species, therefore a mutated from of the prion protein would ail to do this meaning that oxidative species remain in brain tissue causing neuronal damage (Westergard et al, 2007). However Westergard et al (2007) said that these results had failed to become repetitive in other scientific research. Copper may also be involved in the pathogenesis of prion diseases. Copper is a substance necessary to the function of many enzymes (Westergard et al, 2007). Abnormal metabolisms in the body have been linked with many neurodegenerative diseases, it is thought that copper ions can change the properties of the normal prion protein (Westergard, 2007). Hur et al (2002) have reported that iron is involved in neurodegenerative diseases, scientists have shown that the amount of fe3+ is much higher in the brains of scrapie infected people, fe3+ is needed for free radical formation , concluding that there is a link to oxidative stress and neuronal damage therefore contributing to prion diseases (Hur et al, 2002). A role of the immune system in the propagation of prion diseases ahs been studied and suggests that inflammatory processors for example cytokines play a part in causing neuronal damage in prion diseases (Hur et al, 2002). The role of PrPc and the immune system still remains unknown(Hur et al, 2002). Although many hypotheses have been suggested many are still unclear. Other models for example the cells death model which links necrosis and apoptosis to the formation of a prion disease are still unclear further research needs to be done to support this model. To conclude many scientists have found that the PrPsc protein is the main cause of neuronal damage in patients. Mutations have been researched to find out the mutations linked to the disease. It is unclear of the pathogenesis of prion diseases as many hypotheses have been suggested. How prion diseases first arose is still unclear and how they are transmitted is still undergoing scientific research. References Baskakov I.V, Breydo L, 2007, Converting the prion protein: what makes the protein infectious. Cohen.F.E, 1999, Protein Misfolding and prion disease, Academic press. Goldfarb.L.G, 2002, Kuru; the old epidemic in a new mirror, Elsevier. Harris.D.A, True.H.L, 2006, New insights into prion structure and toxicity, Elsevier inc. Hur.K, Kim.J, Choir.S, Choir.E.K, Carp.R, Kim.Y.S, 2002, The pathogenic mechanisms of prion disease, Elsevier science. Hu.W, Kieseir.B, Frohman.E, Eagar.T.N, Rodger.N.R, Hartung.H.P, Stuve, 2007, Prion proteins: Physiological functions and role in neurological disorders, journal of neurological sciences. Mead.S, Whitfield.M.A, Poulter.M, Shah.P, Uphill J, Campbell, Al-Dujaily, Hummerich.H, Beck.J, Mein.C.A, Verzilli.C, Whittaker.J, Alpers.M.P, Collinge.J, 2009, A Novel Protective Prion Protein Variant that Colocalizes with Kuru Exposure, Massachusetts Medical Society. Mikol.J., 1999, Neuropathology of prion diseases, Elsevier science. Soto.C, Sabotio.G.P, Anderes.L, 2002, Cyclic amplification of protein misfolding: application to prion related disorders and beyond, Elsevier science. Westergard.L, Christensen H.M, Harris D.A, 2007, The cellular prion protein (PrPc):Its physiological function in disease, Elsevier. Yull.H.M, Ironside J.W, Head.M.W, 2009, Further characterisation of the prion protein molecular types detectable in the NIBSC Creutzfeldt-Jakob disease brain reference materials, Elsevier science.

Do Video Games Enhance Selective Attention in Children?

Research: Observing children using gaming consoles can be quite entertaining due to their deeply embedded interest and love for video games. Young boys in particular seem to partake in the interactive environment that gaming allows them to join. Whether it’s Nintendo, Xbox, or Playstation, males of all ages always seem so captivated by the virtual world portrayed on their television set. When one focuses on a specific aspect of a scene while ignoring other aspects, such as focusing on the video game you are playing in the same room as many people are speaking, a concept of selective attention is introduced (Wikipedia, 2006).A normal attention span seems to develop in three stages in children. First, the child’s attention is said to be overly exclusive. This is a term used by psychologists to describe attention that is focused on a single object for long periods while tuning out all other stimuli (Child Development Institute, 2006). Second, a child’s attention dev elops to where it is overly inclusive. This refers to a â€Å"wide span of attention that is constantly and rapidly changing from one object to another such as a toddler who is running from one toy to the next never able to stay with any one toy for any period of time† (CDI, 2006).A child who is stuck at this stage might be diagnosed as having attention deficit disorder. Third, the child develops selective attention where he or she is able to shift the focus whenever he or she pleases from being inclusive to being very exclusive. This is considered a mature pattern of focus and concentration which is needed in a classroom setting. Some reasons a child may have poor attention, concentration, and impulse control are due to anxiety, depression, slow psychological development, learning disabilities, lack of sleep, poor nutrition, low motivation, and especially boredom due to lack of challenge (CDI, 2006).Boredom due to a lack of challenge definitely cannot be a characteristic of video games to the male population who spend hours a day playing; especially not the nine year old Austin who I have babysat for or Brian, another boy I know who is ten years old. Video games were first introduced in the 1970s. â€Å"By the end of that decade they had become a preferred childhood leisure activity†¦Ã¢â‚¬ (Cesarone, 1994). Advocates of video games imply that they may be a friendly way of introducing children to computers, and may increase children's hand-eye coordination and attention to detail.

Miracles: Possible of Not

It was not till the Enlightenment that the question began to be seriously asked, as to whether miracles are possible or not. Prior to this miracle was the substance of life in all strata of society, not only the unlettered. Belief in miracles emboldened belief per se. In the age of faith religion was the foundation of life, and belief in miracles indispensable to it. But with the rise of science and rationalism, and the corresponding demise of religion, the aspect of miracle too lost standing in the concerns of people. Where science was poised and eager to explain all observed phenomena, belief in miracles was an obvious casualty. According to David Hume’s definition, a miracle is â€Å"a transgression of a law of nature by a particular volition of the Deity, or by the interposition of some invisible agent† (1993, p. 77). The mere suggestion of a transgression of natural law was beginning to sound like a heresy to scientifically accustomed ears, even though attributed to the Deity. This paper examines the eighteenth century responses to the question of whether miracles or possible or not, and then broadens the scope to include modern and ancient perspectives. Hume was the first to tackle the question squarely, in the chapter titled â€Å"Of Miracles† in the 1948 publication An Enquiry Concerning Human Understanding. From purely metaphysical considerations the conclusion is that miracles are indeed possible. We must remember that the core of Hume’s philosophy is empirical skepticism. The materialists, weaned on the mechanics of Newton, were pronouncing outright miracles impossible. The laws of motion and gravity were successfully explaining the heavenly bodies, and hardly anyone suspected that they were not universal in scope. Newtonian mechanics has no place for miracles. This was almost a proof of the invalidity of miracles. But the proud determinism that they espoused had no philosophical foundation to it. Descartes, and the Cartesians, tried desperately for a metaphysics of materialism, but to know avail. Finally Hume overthrew all the strained Cartesian designs, and advanced a devastating critique of reason, as applied to empirical sense data, to deliver objective knowledge. It turned Enlightenment thinking on its head. Knowledge is not possible, and yet miracles are. The philosophers of materialism were stuck on the question as to how it is at all possible that mind interacts with matter. This is indeed a miracle of the highest order, and Hume cannot help but paint the wonder that is inherent in such an idea: For first: Is there any principle in all nature more mysterious than the union of soul with body; by which a supposed spiritual substance acquires such an influence over a material one, that the most refined thought is able to actuate the grossest matter? (Ibid 43) Hume draws the conclusion that it is quite impossible to describe or explain such a thing. So we cannot talk about interaction at all, not even in the parallel case where one inanimate object imparts momentum to another. We talk about the first body causing motion in the second, but we cannot describe an interaction having taken place between cause and effect. We can only observe that the effect has followed the cause, as if two separated events conjoined in time. There is no necessity that the effect must always follow the cause. If we do come to such a conclusion it can only be due to the fact that we have become accustomed to expect such. He then probes into the situation where the effect is unexpected. It seems that the laws of nature has been violated, and we begin to pronounce that a miracle has occurred. But we are hasty to do so, Hume points out. Just because we expect a certain outcome doesn’t imply that natural law dictates the same. He offers the example of the Indian who has never known snow hails miracle when he sees it falling, because nothing in his experience has prepared him for it. Sometimes our science makes us feel that we know the sum extent of natural law. The essence of Hume’s philosophy is that we do not know natural law, and the extent of out ability, regards knowledge, is to infer from experience. He thus leaves room for divine intervention, for natural law is in the hands of the Almighty, only that Hume is not prone to listen to the tall tales of the coarse and the gullible regarding miracles: Though the Being to whom the miracle is ascribed, be Almighty, it [the miracle] does not, upon that account, become a whit more probable, since it is impossible for us to know the attributes or actions of such a Being, otherwise than from the experience of his productions, in the usual course of nature. This still reduces us to past observations†¦ (Ibid 89) Hume is virulent and protracted in his attack against the popular report of miracles, which he thinks has more to do with base psychology than with proper faith. The common lot is so eager to see miracles that it latches on to any hoax and fraud that comes its way, and this is what Hume finds despicable. Such an attitude is understandable coming from a philosopher of the Enlightenment. However, if he had shown a little more empathy towards the gullible he would have recognized that the yearning for miracle is but a testimony of its preciousness. A Chinese proverb reads: â€Å"The miracle is not to fly in the air, or to walk on the water, but to walk on the earth† (qtd. in Moore, 2006, p. 69). However, it does not feel like a partaking in a miracle while walking the earth in one’s daily odyssey of toil and tears. People need to see explicit miracles only to keep them in touch with the miracle of life itself. Prayer itself, as the Russian novelist Ivan Turgenev puts it, is prayer but for a miracle: â€Å"Every prayer reduces itself to this: ‘Great God grant that twice two be not four’† (qtd. in Andrews, 1987, p. 207). Some scientists are finally coming to accept that miracles are indeed possible. Not in the sense in which Hume described it, who defined a miracle as a violation of natural law. He too insists that natural law cannot be violated, and miracle in that sense is impossible. When we come across a miracle we recognize it as such because it violates natural law, only as far as our limited understanding of natural law is concerned. Experience has taught us to expect nature to behave in certain ways, and for all intents and purposes this is natural law for us, the observer. When we observe the unexpected we feel that natural law has been violated, but it may only a new experience for us, like the Indian that Hume describes as coming across the miracle of snow. Polkinghorne therefore suggests an alternative description of miracle, which is not a violation of nature, but instead â€Å"exploration of a new regime of physical experience† (2001, p. 59). All our expectations derive from custom, says Hume, and therefore our worldview is indeed a science of probabilities. That which we expect to happen is probable, but no one can vouchsafe it as certain. Therefore the door is always left open to the improbable. All miracles must find berth in the bracket of improbability. If Hume put it so before the advent of modern science, at the very frontiers of that same science the verdict came back the same. Scientists are by and large determinists, as regards their philosophy. Indeed, the must be so necessarily, for the method of science, as outlined by Francis Bacon in the seventeenth century, induces from empirical evidence the fixed laws of nature. As he asserts in the New Organon, â€Å"I open and lay out a new and certain path for the mind to proceed in, starting directly from the simple sensuous perception† [italics my own] (7). The entire rationale behind such a method is the promise of certainty, as regards knowledge. All scientists necessarily have this object in view, as followers of the method of Bacon. It is agreed among them that the apex of this science is quantum physics. According to this discipline, there is no certain knowledge, not of an atomic particle’s position, nor of its velocity. The rule is codified in Heisenberg’s principle of uncertainty. It lays out a science of probabilities, with the aid of the highest mathematics and the most advanced principles of physics. Yet the essence of it is exactly the same as what Hume put forward as â€Å"custom†. In conclusion, we declare miracles possible or not depending on how we define a miracle. If we insist that it is a violation of natural law, then we must declare it impossible. On the other hand, if it is a highly improbable event, then it is by definition possible. We must remember that the realm of the improbable contains things beyond our wildest expectations, and therefore if we come across such we may mistake it for a violation of nature. References Andrews, R. (1987). The Routledge Dictionary of Quotations. New York: Routledge. Bacon, F. (2000). The New Organon. L. Jardine, M. Silverthorne (Eds.) Cambridge: Cambridge University Press. Hume, D. (1993). An Enquiry Concerning Human Understanding. E. Steinberg (Ed.) Boston: Hackett Publishing. Moore, D. (2006). Zen Wisdom: Magnetic Quotes and Proverbs. Kennebunkport, ME: Cider Mill Press Book Publishers. Polkinghorne, J. C. (2001). Faith, Science and Understanding. New Haven, CT: Yale University Press.

Web Intelligence And Its Usefulness - 1543 Words

Abstract In the world of Information Technology (IT), there are many areas and disciplinary of research available and Web Intelligence (WI) is one of the new sub disciplinary of Artificial Intelligence (AI) and Advanced IT. When AI and IT is implemented on web it defines WI. WI is used to develop web – empowered system, Wisdom Web, Web Mining, web site automation, etc. In this paper, detail discussion is done on Web Intelligence and its usefulness in developing intelligent web. Many literatures are also discussed related to the Web Intelligence and at the end challenges and problems faced during the research in the area is also mentioned. This paper will provide the pathway to the researcher who want to perform research in the field of Web Intelligence. Keywords – Natural Language Processing, Web Intelligence, Artificial Intelligence, Advanced Information Technology I. 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